Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: TN-401.
- Who it may be relevant to
- Registry conditions: Arrhythmogenic Right Ventricular Cardiomyopathy. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
First-in-Human, Open-Label, Safety, Tolerability, Dose-Finding, Pharmacodynamic and Cardiac Transgene Expression Study of TN-401, a Recombinant Adeno-associated Virus Serotype 9 (AAV9) Containing Plakophilin-2 (PKP2) Transgene, in Adults With PKP2 Mutation-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Overview
This first-in-human study is designed to evaluate the safety, and preliminary efficacy (PD) of TN-401 gene therapy in adult patients with symptomatic PKP2 mutation-associated ARVC.
Detailed description
The RIDGE-1™ open-label Safety, Tolerability, Dose-finding, PD and Cardiac Transgene Expression Study will enroll up to 15 patients in two planned dose cohorts. Patients in each cohort will receive a single intravenous (IV) dose of TN-401. Following Data Safety Monitoring Board (DSMB) review of each dose cohort, the next dose cohort will be initiated. DSMB review will also be needed to expand the dose cohorts. The dose for Cohorts 1/1a will be 3E13 (3 × 1013) vg/kg and the dose for Cohorts 2/2a will be 6E13 (6 × 1013) vg/kg.
Interventions
- Genetic TN-401
TN-401 is a recombinant adeno-associated virus serotype 9 (AAV9) gene therapy containing Plakophilin-2 (PKP2) transgene. It is a single (one-time) intravenous dose.
Primary outcome measures
- Number and severity of Adverse Events over the course of the study. [Time frame: 52 weeks]
- Number of Serious Adverse Events related to study drug. [Time frame: 5 years]
Secondary outcome measures (3)
- To assess changes in daily PVC and NSVT counts [Time frame: Week 52]
- To assess frequency of ICD therapy administration [Time frame: Week 52]
- To assess frequency of sustained VT [Time frame: Week 52]
Eligibility criteria
Inclusion criteria
- PKP2 mutation (pathogenic or likely pathogenic)
- Arrhythmogenic Right Ventricular Cardiomyopathy as defined by the 2010 revised Task Force Criteria
- Left Ventricular Ejection Fraction ≥50%
- Functioning Implantable Cardiac Defibrillator with remote integration capabilities at least 9 months prior to Screening
- NYHA Functional Class I, II, or III
- Frequent premature ventricular contractions (PVCs)
Exclusion criteria
- Ventricular tachycardia (VT) ablation within 6 months of Screening or planned VT ablation within 6 months after Screening
- High AAV9 neutralizing antibody titer
- Prior myocardial infarction
- Right Ventricular Heart Failure
- Class IV Heart Failure
- Clinically significant renal disease
- Clinically significant liver disease
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 7 centers
- University of California San Francisco — San Francisco
- University of Colorado - Anschutz Medical Campus — Aurora
- Johns Hopkins University — Baltimore
- Brigham and Women's Hospital — Boston
- Mayo Clinic — Rochester
- NYU Langone Health — New York
- Cleveland Clinic — Cleveland
Identifiers
NCT: NCT06228924 · TN-401-0012